Project Summary/Abstract Approximately 2/3 of laboring women receive supplemental oxygen (O2) in an attempt to reverse perceived fetal hypoxia on electronic fetal monitoring (EFM). O2 supplementation is most commonly used in patients with Category II EFM, a class of EFM patterns designed in part to identify fetal acidemia. This liberal use of O2 in laboring patients is concerning because hyperoxygenation in infants is associated with adverse outcomes including retinopathy and abnormal neurodevelopment. Furthermore, excess O2 exposure is linked to free radical generation and subsequent oxidative cell damage. This calls for a closer look at the safety of intrauterine O2 exposure. The proposed project explores potential mechanisms for harm with maternal O2 supplementation in laboring patients with Category II EFM. Specifically, this project will determine the effect of O2, compared to room air (RA), on umbilical cord and maternal serum levels of malondialdehyde (MDA) and 4-hydroxynonenal (4- HNE), markers of free radical-induced oxidative stress. The study will also explore the feasibility of using urine markers of oxidative stress as a less invasive alternative to serum markers and to establish temporal trends in oxidative stress throughout labor. This project will employ a randomized controlled design based on a recently completed pilot trial that demonstrated feasibility of such an approach. The expected outcome of this study is high-quality, mechanistic, pilot data on the pathophysiology of in-utero O2 exposure. If the central hypothesis that intrauterine exposure to O2 during labor is less safe than RA is confirmed, the findings will impact the intrapartum management of millions of patients who labor and deliver each year in the United States. Ultimately, this work will lead to evidence-based intrauterine resuscitation during labor that minimizes neonatal morbidity.